The long term goal of this application is to determine how glucocorticoids regulate the expression of the pro-apoptotic gene Bnip3 in the developing rat brain. Central nervous system development uses apoptosis as a normal developmental process to eliminate excess cells. Bnip3, a pro-apoptotic gene, is highly expressed within the developing rat cortex and is upregulated by the synthetic glucocorticoid, dexamethasone. Clinical studies have shown several lines of research, which suggest that glucocorticoid regulation of Bnip3 may play a role in neonatal brain pathology. We anticipate the proposed experiments will provide pre-clinical evidence for some mechanisms involved in glucocorticoid endangerment of developing neurons. Upon completion of the proposed experiments we will determine if glucocorticoid treatment alters developmental gene expression of Bnip3 mRNA and protein in the rat cortex. Also, we will determine if glucocorticoids act directly on cortical neurons to regulate Bnip3 expression and finally we will determine if the Bnip3 promoter is directly regulated by glucocorticoid receptors.